Carotenoids and retinoids are naturally occurring substances which contain extensively conjugated polyene chains. Carotenoids have the most extensively conjugated systems of carbon-carbon double bonds which give rise to their many varied and brilliant colors. Many carotenoids and retinoids, which are naturally occurring substances, are biologically active. For example, carotenoids and retinoids have been shown to retard the development of some experimentally induced animal tumors (N. I. Krinsky, Annu. Rev. Nutr., 13, 561–587 (1993); Matthews-Roth, Curr. Top. Nutr. Dis., 22:17–38 (1989)). Furthermore, epidemiological evidence indicates that carotenoid intake correlates inversely with the incidence of some types of cancer (Peto et al, Nature, 290:201–208 (1981)). Clinical data have demonstrated that related compounds, retinoic acid, retinol and retinamides, can be used to prevent and treat cancers of the skin, head and neck, lung and bladder, acute promyelocytic leukemia, leukoplakia and myelodysplastic syndromes (see, for example, D. L. Hill and C. J. Grubs, Annu. Rev. Nutr., 12:161–181 (1992)).
Carotenoids, retinoids and related conjugated polyenes are reactive towards molecular oxygen (O2). β-carotene has been shown to have antioxidant properties at the low oxygen pressures found in tissues (see, for example, Burton and Ingold, Science, 224:569–573 (1984)). Carotenoids are more reactive than retinoids towards oxygen because of their larger, more extensively conjugated system of double bonds. The products of such oxidative degradation of carotenoids retinoids, and related conjugated polyenes and their potential physiological activities have, nevertheless, received remarkably little attention, with the exception of vitamin A, which is obtained as a product of the biological oxidation of β-carotene.
Mordi examined the products formed during the self-initiated autoxidation of β-carotene (see Mordi et al, Tetrahedron Letters, 32(33):4203–4206 (1991)). The main products identified in the early stages of β-carotene autoxidation, predominantly short chain carbonyl compounds, are epoxides, β-ionone, β-apo-13-carotenone, retinal, and related carbonyl compounds. The self-initiated oxidation of β-carotene with molecular oxygen has also been shown to produce epoxides, dihydrofurans, carbonyl compounds, carbon dioxide, traces of alcohols, and some other compounds (see Mordi et al, Tetrahedron Vol. 49(4):911–928 (1993)). The later paper, makes a mention of some polymeric/oligomeric material which frequently deposited out of solution, particularly in the later stages of β-carotene oxidation.
There exists a need for improved cancer therapeutics.